The principal long-range goal is the development of methods for the total synthesis of biologically functional genes and to understand molecular mechanisms of gene control and expression. The total research involved in this program can be categorized as follows: (1) Further development of the chemical methods for the synthesis of deoxyribonucleotides. (2) Structure-function relationships in the totally synthetic tyrosine tRNA gene. a. Mechanism of the initial recognition of the promoter region by the RNA polymerase. b. Formation of the stable DNA-RNA polymerase complex. c. The initiation of transcription by the RNA polymerase. (3) Synthesis of a variety of promoters with carefully designed alterations in nucleotide sequences will be used to study the transcription mechanism. (4) Cloning of the totally synthetic gene in suitable plasmids and vectors for work on structure-function relationships. (5) Studies of the DNA-membrane interaction in bacterial and mammalian synthesis. (6) Studies of the DNA-protein interactions using enveloped viruses such as PM2, vesicular stomatitis virus (V.S.V.) and sindbis virus.